INDUCTION IN-VITRO OF A PRIMARY HUMAN ANTIVIRAL CYTOTOXIC T-CELL RESPONSE

We report herein the successful priming of human anti-viral cytotoxic T cells (CTL) in vitro using two induction strategies based on the sti mulation of peripheral blood mononuclear cells isolated from uninfecte d donors with synthetic viral peptides. The peptides used contain HLA- A2 binding motifs and have been identified as HLA-A2-restricted CTL ep itopes in patients infected by the hepatitis B and C viruses. One appr oach uses repetitive long-term stimulation and the other uses bulk cul tures containing large numbers of naive peripheral blood mononuclear c ells. Both approaches successfully induce HLA-A2-restricted CTL specif ic for several viral epitopes. Some CTL recognize endogenously synthes ized antigen on target cells infected with recombinant vaccinia virus expressing the corresponding viral proteins. This simple technique per mits easy analysis of the primary human CTL repertoire, and may be exp loitable for production of specific CTL effector cells for adoptive im munotherapy and dissection of the cellular and molecular requirements for priming of naive human CTL.